Immunodiagnosis of Neurocysticercosis: Ways to Focus on the Challenge

Abstract

Neurocysticercosis (NCC) is a disease of the central nervous system that is considered a public health problem in endemic areas. The definitive diagnosis of this disease is made using a combination of tools that include imaging of the brain and immunodiagnostic tests, but the facilities for performing them are usually not available in endemic areas. The immunodiagnosis of NCC is a useful tool that can provide important information on whether a patient is infected or not, but it presents many drawbacks as not all infected patients can be detected. These tests rely on purified or semipurified antigens that are sometimes difficult to prepare. Recent efforts have focused on the production of recombinant or synthetic antigens for the immunodiagnosis of NCC and interesting studies propose the use of new elements as nanobodies for diagnostic purposes. However, an immunodiagnostic test that can be considered as “gold standard” has not been developed so far. The complex nature of cysticercotic disease and the simplicity of common immunological assumptions involved explain the low scores and reproducibility of immunotests in the diagnosis of NCC. Here, the most important efforts for developing an immunodiagnostic test of NCC are listed and discussed. A more punctilious strategy based on the design of panels of confirmed positive and negative samples, the use of blind tests, and a worldwide effort is proposed in order to develop an immunodiagnostic test that can provide comparable results. The identification of a set of specific and representative antigens of T. solium and a thorough compilation of the many forms of antibody response of humans to the many forms of T. solium disease are also stressed as necessary.

Immunological and molecular diagnosis of cysticercosis

“…90,91 As proposed by EsquivelVelazquez et al, in 2011, new tools like phage display peptide selection, production of synthetic, and recombinant antigens, could permit us to shorten the path to identify specific antigens capable to distinguish not only the stages of the parasite, but also exposure from viable and non-viable infection. 92 In this way, a good alternative to distinguish exposure from infection could be the use of oncospheral antigens, which to date have mostly been used as vaccine candidates. The 8 kDa antigens seem to be promising candidates to distinguish viable from nonviable NCC; however, the sensitivity of these assays needs improving.…”

Neurocysticercosis: is serology useful in the absence of brain imaging?

“…Perhaps due to raised awareness of the extent of the problem, the claim for an accurate serological screening tool for human cysticercosis is a frequent topic in the literature (Dorny et al. 2003; Esquivel‐Velazquez et al. 2011).…”

Immunodiagnosis Tools for Parasitic Diseases

“…Now a days multiple antigens have been used and among them, main are low molecular mass (LMM) antigens, excretory/secretory (ES), crude soluble extract (CSE), total saline extract, antigen B, lentil lectin glycoproteins (LLGPs), vesicular fluid (VF), membrane and scolex extracts, somatic antigens, recombinant proteins, and synthetic peptides. Multiple methods used to date for the immunodiagnosis of NCC like complement fixation, agglutination, radio immune assays, ELISA and Western Blot (WB) can be counted [33]. LLGP-WB has a sensitivity of >90% and a specificity of 100%.…”

“…In Indian patients almost two thirds of the NCC patients have an SCG; LLGPs have shown to be less sensitive than for multiple cysticerci. Antigen for immunodiagnosis from the members of the 8 kDa family, Ts18var1 has been produced in insect cells as well as TsRs1, Ts18var1, and Ts18 Var3; the 14 and 18 kDa proteins produced by recombination; Ts14, Ts18var1, TSRS1 and TSRS2var1 by chemical synthesis, and full-length Ts18 and Ts14 by chemical ligation, Ag1V1/Ag2 by recombination as well as Ts8B1, Ts8B2, Ts8B3, Ts14 and a 10 kDa protein, GP50, which is not a member of the 8 kDa family but it is part of the LLGPs, was produced by recombination in bacteria and in a baculovirus expression system [33][34][35][36][37][38][39]. Outside from LLGPs other proteins that have also been produced or synthesized include T24 (integral membrane protein that does not bind to lentil lectin) produced in a drosophila cell line; HP6-Tsag (oncospheral adhesion protein of Taenia saginata) in bacteria and baculovirus systems with similar specificities between the systems (93-95%), but higher sensitivity for the inactive cases by the baculovirus protein (48-64%); peptide NC-1 selected by phage-display; peptides KETc12, 410 and 413 synthesized from a cDNA library of T. crassiceps and recombinant TS24 and Es33.…”

“…Outside from LLGPs other proteins that have also been produced or synthesized include T24 (integral membrane protein that does not bind to lentil lectin) produced in a drosophila cell line; HP6-Tsag (oncospheral adhesion protein of Taenia saginata) in bacteria and baculovirus systems with similar specificities between the systems (93-95%), but higher sensitivity for the inactive cases by the baculovirus protein (48-64%); peptide NC-1 selected by phage-display; peptides KETc12, 410 and 413 synthesized from a cDNA library of T. crassiceps and recombinant TS24 and Es33. The methods of production are varied, as well as the results and the ways to evaluate the produced protein, some giving very good sensitivities but in other cases, the native protein is much better than the produced one [33].…”